Reticuloendothelial phagocytic function was evaluated following surgery, trauma and sepsis. Emphasis was placed on the role of opsonic protein, referred to as opsonic alpha-2-surface-binding glycoprotein, in regulating reticuloendothelial phagocytic activity. Reticuloendothelial depression was observed early following injury and the degree of RE depression is related to the degree of injury. Opsonic deficiency following surgery and trauma appears etiologic in the genesis of reticuloendothelial phagocytic depression, while restoration of opsonin levels correlates with RE recovery. The purified protein has been biochemically characterized. It is identical to cold-insoluble globulin or plasma fibronectin. An immunoassay for the protein has been developed and utilized for both animal and clinical studies. Opsonic deficiency by both bioassay and immunoassay has been documented in trauma and burn patients, especially during sepsis and organ failure. Opsonic deficiency correlated with failure in host defense mechanisms and cardiovascular and pulmonary dysfunction. The common identity of opsonic glycoprotein and cold-insoluble globulin suggests the use of cryoprecipitate for replacement therapy. Administration of cryoprecipitate reverses opsonic deficiency in injured septic patients and improves cardiovascular and pulmonary function. In animal studies, intraveous administration of cryoprecipitate or the purified opsonic protein will prevent opsonic deficiency following surgery and restore reticuloendothelial clearance of blood-borne particulates. Parallel studies with disseminated intravascular coagulation, experimental trauma, or sepsis, all demonstrate that liver and spleen phagocytic clearance depression results in increased extrahepatic localization, especially in the lungs. It is hypothesized thus, that reticuloendothelial systemic host defense may be important in cardiovascular and pulmonary function following trauma. Reversal of opsonic deficiency may be a potential new modality of therapy for treatment of the injured septic patient with organ failure.